Regenerative Medicine: Emerging Techniques to Translation Approaches

Preface
Acknowledgements
Contents
Editors and Contributors
1: Regeneration and Tissue Microenvironment
1.1 Introduction
1.2 Role of Tissue Microenvironment
1.2.1 Cells
1.2.1.1 Stem Cells
1.2.1.2 Fibroblasts
1.2.1.3 Immune Cells
1.2.1.4 Platelets
1.2.2 Extracellular Matrix
1.2.2.1 Collagen
1.2.2.2 Fibronectin
1.2.2.3 Glycosaminoglycans (GAGs)
1.2.2.4 Proteoglycans
1.2.3 Soluble Signaling Molecules
1.3 Regeneration
1.4 Conclusion
References
2: Non-stem Cell Mediated Tissue Regeneration and Repair
2.1 Introduction
2.1.1 Regeneration and Repair: Are They the Same?
2.1.2 Stem Cells and Tissue Repair
2.1.3 Stem Cells vs. Non-stem Cells
2.1.3.1 Stem Cells
2.1.3.2 Non-stem Cells
2.1.4 Regenerative Medicine Beyond the Stem Cells
2.2 Types of Non-stem Cell Mediated Regeneration and Repair
2.2.1 Naturally Occurring
2.2.1.1 Olfactory Ensheathing Cells (OECs)
2.2.1.2 Schwann Cells
2.2.1.3 Epithelial Basal Cells
2.2.1.4 Endothelial Progenitor Cells
2.2.1.5 Precursor or ``-Blast´´ Cells
2.2.1.6 Satellite Cells
2.2.2 Clinically Available
2.2.2.1 Cellular Approaches
2.2.2.2 Acellular Approaches
2.2.3 Under Exploration
2.2.3.1 Cellular Approaches
Nullipotent Cells
Blast or Precursor Cells
2.2.3.2 Acellular Approaches
2.2.3.3 Combination Based
2.3 Conclusion
References
3: Immunological Perspectives Involved in Tissue Engineering
3.1 Introduction
3.2 Biomaterials and Tissue Engineering
3.2.1 Metallic Biomaterials
3.2.2 Ceramic Biomaterials
3.2.3 Polymer Biomaterials
3.3 Immunological Response to Biomaterials Used in Tissue Engineering
3.3.1 Innate Immune Response to Biomaterials
3.3.2 Adaptive Immune Response to Biomaterials
3.4 Need for Graft and Their Interaction with the Recipient´s Immune System
3.5 Modulation of the Host Immune Response by Biomaterials
3.5.1 Immune Pathways Modulated by Foreign Molecules and Biomaterials
3.5.2 Macrophage Polarization-Mediated Immune Modulation
3.5.3 Immune Responses to Nanomaterials in Tissue Engineering
3.5.4 Immunomodulation by Stem Cells Used in Engineered Tissue
3.6 Future Perspectives and Conclusion
References
4: Advances in Medical Imaging for Wound Repair and Regenerative Medicine
4.1 Need for Imaging
4.2 The Process of Skin Wound Healing
4.3 Scar Fibrosis
4.4 Imaging in Wound Healing
4.4.1 Surface Imaging (Digital Photography)
4.4.2 Optical Coherence Tomography
4.4.3 Laser Doppler Imaging (LDI)
4.4.4 Laser Speckle Imaging (LSI)
4.4.5 Fluorescence Imaging
4.4.6 Spectral Imaging
4.4.7 Ultrasonography
4.4.8 Photoacoustic Imaging (PAI)
4.4.9 Thermal Imaging
4.5 Prospects for Advancements in Current Systems for Assessment of Healing
4.5.1 Imaging for Biochemical Analysis of Wounds by Micro-spectroscopy
4.5.2 Monitoring Drug Delivery for Identifying Therapeutic Efficacy
References
5: Role of Biosensors in Regenerative Therapeutics: Past, Present, and Future Prospects
5.1 Introduction
5.2 Envisaging Direction in Regenerative Medicine
5.3 Recent Perspective into the Role of Stromal Cell in Regenerative Medicine
5.4 General Biosensing Technologies
5.5 Biomarkers in Regenerative Medicine
5.6 Conventional Strategies for Sensing of Biomolecules
5.7 Biosensors in Regenerative Medicine
5.7.1 Biosensors to Detect Pluripotent Stromal Cells
5.7.2 Biosensor Prospect in Cartilage Regeneration
5.7.3 Biosensor for Prolotherapy
5.7.4 Regenerative Medicine On Chip
5.8 Nanotechnology in Regenerative Medicine
5.9 Bioprocess Control and Therapeutic Applications in Regenerative Medicine
5.10 Conclusions
References
6: Acute and Chronic Wound Management: Assessment, Therapy and Monitoring Strategies
6.1 Introduction
6.2 Physiology of Wound Healing
6.2.1 Factors Affecting Wound Healing
6.3 Challenges Faced in the Wound Healing Procedure
6.4 Therapeutic Strategies
6.4.1 Traditional Methods
6.4.1.1 Debridement and Dressing
6.4.1.2 Skin Grafts
6.4.1.3 Hyperbaric Oxygen Therapy
6.4.1.4 Negative Pressure Wound Therapy (NPWT)
6.4.2 Advanced and Emerging Methods
6.4.2.1 Tissue Engineered Grafting
6.4.2.2 Genetic Editing (miRNA)
6.4.2.3 Phototreatment
6.4.2.4 Magnetic Therapy
6.4.2.5 Microwave Therapy
6.4.2.6 Nanotechnology for Wound Therapy
6.5 Assessment and Monitoring Wound Healing
6.5.1 Invasive Assessment Techniques
6.5.2 Non-invasive Assessment Techniques
6.5.2.1 OCT Imaging
6.5.2.2 High-Frequency Ultrasound Imaging
6.5.3 Wound Healing Models and Quantitative Analysis of the Wounds
6.6 Conclusion
References
7: Stem Cells and Therapies in Cardiac Regeneration
7.1 Cardiac Regeneration
7.1.1 Cardiomyocyte Loss During Myocardial Infarction
7.1.2 Cell Cycle and Cardiomyocyte Proliferation
7.1.3 Stem Cells as a Model for Cardiac Regeneration
7.1.3.1 Multipotent Stem Cells
Fetal Stem Cells
Adult Stem Cells
Cardiac Stem Cells
7.1.3.2 Pluripotent Stem Cells
Embryonic Stem Cells
Induced Pluripotent Stem Cells
7.2 Noncoding RNAs and Cardiac Regeneration
References
8: Hydrogel-Based Tissue-Mimics for Vascular Regeneration and Tumor Angiogenesis
8.1 Introduction
8.2 Microenvironmental Considerations for Vascular Regeneration
8.3 Microenvironmental Considerations for Tumor Angiogenesis
8.4 Hydrogel-Based Models for Vascular Regeneration and Tumor Angiogenesis
8.4.1 Matrigel
8.4.2 Collagen and Gelatin
8.4.3 Fibrin
8.4.4 Alginate and Agarose
8.4.5 Other Natural Materials
8.4.6 Poly(ethylene Glycol)
8.4.7 Poly(lactic-co-Glycolic Acid) and Poly(caprolactone)
8.4.8 Hybrid Hydrogels
8.5 Biofabrication Strategies for Vasculogenesis and Angiogenesis
8.5.1 Self-Assembly
8.5.2 Bioprinting
8.5.3 Electrospinning
8.5.4 Micromolding
8.5.5 Photolithography and Laser-Based Techniques
8.6 Conclusions
References
9: Advances in 3D Printing Technology for Tissue Engineering
9.1 Introduction
9.2 Printing Technology
9.2.1 Laser-Assisted
9.2.2 Laser-Induced Printing
9.2.3 Laser-Guided Printing
9.2.4 Stereolithography Apparatus (SLA)
9.2.5 Digital Light Projection (DLP)
9.2.6 Two-Photon Polymerization (TPP)
9.2.7 Extrusion-Based Printing System
9.2.8 Inkjet Printing System
9.3 Types of Biomaterial Inks Used in 3D Printing
9.3.1 Polymer-Based Inks
9.3.2 Ceramic-Based Inks
9.3.3 Composite Inks
9.4 Application of 3D Printing in Tissue Engineering
9.4.1 Nervous Tissue
9.4.2 Liver
9.4.3 Kidney
9.4.4 Skin
9.4.5 Bone and Cartilage
9.4.6 Ocular Tissues
9.4.7 Ears
9.5 Conclusion
References
10: Adult Neurogenesis: A Potential Target for Regenerative Medicine
10.1 History of Adult Neurogenesis
10.2 Factors Influencing Adult Neurogenesis
10.3 Anatomical and Physiological Properties of Adult Formed Neurons
10.3.1 Distinct Timeline of Evolution of Morphological Features in Adult Formed Neurons
Box 10.1 Species Specific Differences of Adult Formed Neurons
10.3.2 Physiological Features of Adult Formed Neurons
10.4 Functional Roles of Adult Neurogenesis
10.4.1 Learning and Memory
10.4.2 Pattern Separation and Pattern Completion
10.4.3 Higher Order Cognitive Functionalities
10.5 Adult Neurogenesis: A Target for Regenerative Medicine
10.5.1 Stroke and Injuries
10.5.2 Neurodegenerative Conditions
10.5.3 Neuropsychiatric Conditions
10.5.4 Potential Roles in Learning and Cognitive Functionalities
Box 10.2 Outstanding Questions and Future Directions
References
11: Regenerative Approaches in the Nervous System
11.1 Background
11.1.1 Anatomy and Organisation of the Nervous System
11.1.2 Function of the Nervous System
11.1.3 Barriers Protecting the CNS
11.1.4 Pathophysiology of Nervous System Injuries
11.2 Issues with Natural Regeneration and Repair
11.2.1 CNIs
11.2.2 PNI
11.2.3 Potential Strategies for Regeneration and Repair
11.3 Current Approaches for Clinical Management
11.3.1 Brain Injury
11.3.1.1 Diagnostics
11.3.2 Spinal Cord Injury
11.3.2.1 Diagnostics
11.3.2.2 Management
11.3.3 Peripheral Nerve Injury
11.3.3.1 Diagnostics
11.3.3.2 Management
11.4 Novel Regenerative Approaches
11.4.1 Brain Injury
11.4.1.1 Cell Transplantation-Based Approaches
11.4.1.2 Biomaterial-Based Approaches
11.4.1.3 Bioactive Molecule-Based Approaches
11.4.2 Spinal Cord Injury
11.4.2.1 Cell Transplantation-Based Approaches
11.4.2.2 Biomaterial-Based Approaches
11.4.2.3 Bioactive Molecule-Based Approaches
11.4.2.4 Combination-Based Approaches
11.4.3 Peripheral Nerve Injury
11.4.3.1 Cell-Based Approaches
11.4.3.2 Biomaterial-Based Approaches
11.4.3.3 Bioactive Molecule-Based Approaches
11.4.3.4 Combination-Based and Other Approaches
11.5 Translational Needs
References
12: Prenatal Interventions for the Treatment of Congenital Disorders
12.1 Introduction
12.2 Technological Advances in Early Diagnosis
12.3 Prenatal Pharmacotherapy
12.4 Prenatal Surgery
12.5 Prenatal Cell Therapy
12.6 Prenatal Gene Therapy and Gene Editing
12.7 Future Direction and Implications
References
13: Understanding LncRNAs in Biomaterials Development for Osteointegration
13.1 Osseointegration Processes
13.1.1 Blood Clot Formation
13.1.2 Immune Responses, Angiogenesis, and Osteogenesis
13.2 LncRNAs and Their Functions
13.2.1 Characteristics and Classification of LncRNAs
13.2.2 Biological Functions of LncRNAs
13.2.3 Action Mechanisms of LncRNAs
13.2.3.1 Epigenetic Regulation
13.2.3.2 Transcriptional Regulation
13.2.3.3 Post-transcriptional Regulation
13.3 LncRNAs in the Blood Clot and Osseointegration
13.3.1 Blood Clot Feature and Osseointegration Mediated by Nano-dimensional Implant Surfaces
13.3.2 LncRNAs in Blood Clots Mediated by Nano-dimensional Implant Surfaces
13.4 Summary and Perspective
References
14: Current Approaches in Vertical Bone Augmentation and Large Bone Deficiencies in the Orofacial Region
14.1 Introduction
14.2 Vertical Bone Augmentation
14.2.1 Clinical Problem
14.2.2 Current Surgical Approaches and Limitations
14.2.3 Additive Manufacturing Strategies for Vertical Bone Augmentation
14.2.3.1 Additively Manufactured Bioceramic Scaffolds
14.2.3.2 Additively Manufactured Polymeric Constructs
14.3 Large Bone Volume Deficiencies: Orofacial Regenerative Medicine
14.3.1 Current Approaches
14.3.2 Additive Manufacturing and Other Experimental Techniques
14.3.3 Future Directions
References
15: In-Vitro and In-Vivo Tracking of Cell-Biomaterial Interaction to Monitor the Process of Bone Regeneration
15.1 Introduction
15.2 Significance of Tracking Bone-Biomaterial Interaction
15.3 In-Vitro Evaluation Methods
15.3.1 Cytotoxicity and Cell Metabolic Activity
15.3.2 Hemocompatibility and Immunogenic Response
15.3.3 Cellular Adhesion and Proliferation
15.3.4 Osteogenic Differentiation
15.4 In-Vivo Evaluation Methods
15.4.1 Inflammatory Response
15.4.2 Biomechanics
15.4.3 Histomorphometry and Immunohistochemistry to Evaluate Osteoblast and Osteoclast Response
15.4.4 In-Vivo Imaging for Bone Tissue Engineering
15.5 In-Silico Evaluation Methods
15.6 Future Directions
References
16: The Prospects of RNAs and Common Significant Pathways in Cancer Therapy and Regenerative Medicine
16.1 Introduction
16.1.1 Similarities and Differences Between Cancer and Regeneration
16.1.2 Significant Pathways of Regeneration and Cancer
16.2 Cell Cycle and Checkpoints
16.3 Regulatory Proteins in Cell Division
16.3.1 Cyclins and CDK
16.3.1.1 Cyclins and CDK in Cancer
16.3.1.2 Cyclins and CDKs in Regeneration
16.3.2 E2F
16.3.2.1 E2F Transcription Factor in Cancer
16.3.2.2 E2F Transcription Factor in Regeneration
16.3.3 eIF
16.3.3.1 eIF in Cancer
16.3.3.2 eIF Transcription Factor in Regeneration
16.3.4 Caspases
16.3.4.1 Caspases in Cancer
16.3.4.2 Caspases in Regeneration
16.3.5 mTOR
16.3.5.1 mTOR in Cancer
16.3.5.2 mTOR in Regeneration
16.4 Genes Regulating Cell Division
16.4.1 p53
16.4.1.1 p53 in Cancer
16.4.1.2 p53 in Regeneration
16.4.2 p21
16.4.2.1 p21 in Cancer
16.4.2.2 p21 in Regeneration
16.4.3 Yamanaka Factors
16.4.3.1 Yamanaka Factors in Cancer
16.4.3.2 Yamanaka Cocktail in Regeneration
16.4.4 NANOG
16.4.4.1 NANOG in Cancer
16.4.4.2 Nanog in Regeneration
16.4.5 Hox Genes
16.4.5.1 HOX Genes in Cancer
16.4.5.2 HOX Genes in Regeneration
16.5 Pathways Regulating Cell Division
16.5.1 Hippo Pathway
16.5.1.1 Hippo Pathway in Cancer
16.5.1.2 Hippo Pathway in Regeneration
16.5.2 JAK-STAT Pathway
16.5.2.1 JAK-STAT Pathway in Cancer
16.5.2.2 JAK-STAT Pathway in Regeneration
16.5.3 PI3K Pathway
16.5.3.1 PI3K Pathway in Cancer
16.5.3.2 PI3K Pathway in Regeneration
16.5.4 Ras-Raf-ERK Pathway
16.5.4.1 Ras-Raf-ERK Pathway in Cancer
16.5.4.2 Ras-Raf-ERK Pathway in Regeneration
16.5.5 Wnt Pathway
16.5.5.1 Wnt Signalling Pathway in Cancer
16.5.5.2 Wnt Signalling Pathway in Regeneration
16.6 Influence of Microenvironment
16.6.1 DNA Methylation and Epigenetic Regulation in Cancer
16.6.2 Role of DNA Methylation and Epigenetics in Regeneration
16.6.3 Role of Extracellular Matrix in Cancer
16.6.4 Role of Extracellular Matrix in Regeneration
16.6.5 Inflammation
16.6.5.1 Role of Inflammation in Cancer
16.6.5.2 Role of Inflammation in Regeneration
16.7 Growth Factors
16.7.1 Growth Factor Receptor in Cancer
16.7.2 Growth Factors in Regeneration
16.7.2.1 Transforming Growth Factor Beta (TGF-beta)
16.7.2.2 Fibroblast Growth Factor (FGF)
16.8 Autophagy
16.8.1 Autophagy in Cancer
16.8.2 Autophagy in Regeneration
16.9 miRNA
16.9.1 miRNAs in Cancer
16.9.2 miRNAs in Regeneration
16.10 Applied Therapeutics
16.10.1 Regenerative Medicine
16.10.2 Cancer Therapy
16.11 Biomaterial-Based Therapies
16.12 Newer Therapeutic Aspects
16.12.1 Gene Therapy
16.12.2 RNA-Based Therapy
16.12.3 Gene Delivery System
16.12.3.1 Viral Vectors
16.12.3.2 Non-Viral Vectors
Electroporation
Gene Gun
Inorganic Particles
Lipid-Based Therapy
Polymer-Based Therapy
16.13 Cell Therapy
16.13.1 Stem Cell Therapy
16.13.2 CAR-T Cells Therapy
16.13.3 NK Cells-Based Therapy
16.14 Conclusion
References